EP2895744A1 - Syringe pump system for pulse-free metering and precise mixing in hplc, uhplc, micro-hplc and nano-hplc - Google Patents

Syringe pump system for pulse-free metering and precise mixing in hplc, uhplc, micro-hplc and nano-hplc

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Publication number
EP2895744A1
EP2895744A1 EP13789166.9A EP13789166A EP2895744A1 EP 2895744 A1 EP2895744 A1 EP 2895744A1 EP 13789166 A EP13789166 A EP 13789166A EP 2895744 A1 EP2895744 A1 EP 2895744A1
Authority
EP
European Patent Office
Prior art keywords
pump
hplc
syringe
pressure
valve
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP13789166.9A
Other languages
German (de)
French (fr)
Other versions
EP2895744B1 (en
Inventor
Werner DÖBELIN
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DOEBELIN, WERNER
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Individual
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Publication date
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Publication of EP2895744A1 publication Critical patent/EP2895744A1/en
Application granted granted Critical
Publication of EP2895744B1 publication Critical patent/EP2895744B1/en
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Anticipated expiration legal-status Critical

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B11/00—Equalisation of pulses, e.g. by use of air vessels; Counteracting cavitation
    • F04B11/005—Equalisation of pulses, e.g. by use of air vessels; Counteracting cavitation using two or more pumping pistons
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B1/00—Multi-cylinder machines or pumps characterised by number or arrangement of cylinders
    • F04B1/02—Multi-cylinder machines or pumps characterised by number or arrangement of cylinders having two cylinders
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B13/00—Pumps specially modified to deliver fixed or variable measured quantities
    • F04B13/02—Pumps specially modified to deliver fixed or variable measured quantities of two or more fluids at the same time
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B17/00—Pumps characterised by combination with, or adaptation to, specific driving engines or motors
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B23/00—Pumping installations or systems
    • F04B23/04—Combinations of two or more pumps
    • F04B23/06—Combinations of two or more pumps the pumps being all of reciprocating positive-displacement type
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B37/00—Pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B25/00 - F04B35/00
    • F04B37/10—Pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B25/00 - F04B35/00 for special use
    • F04B37/12—Pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B25/00 - F04B35/00 for special use to obtain high pressure
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B53/00—Component parts, details or accessories not provided for in, or of interest apart from, groups F04B1/00 - F04B23/00 or F04B39/00 - F04B47/00
    • F04B53/10—Valves; Arrangement of valves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B53/00—Component parts, details or accessories not provided for in, or of interest apart from, groups F04B1/00 - F04B23/00 or F04B39/00 - F04B47/00
    • F04B53/14—Pistons, piston-rods or piston-rod connections
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B53/00—Component parts, details or accessories not provided for in, or of interest apart from, groups F04B1/00 - F04B23/00 or F04B39/00 - F04B47/00
    • F04B53/16—Casings; Cylinders; Cylinder liners or heads; Fluid connections
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/20—Injection using a sampling valve
    • G01N2030/201—Injection using a sampling valve multiport valves, i.e. having more than two ports
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/16—Injection
    • G01N30/20—Injection using a sampling valve
    • G01N2030/202—Injection using a sampling valve rotary valves

Definitions

  • Syringe pump system for pulsation-free dosing and accurate mixing in HPLC, UHPLC, nano- and micro-HPLC
  • the invention relates to a syringe pump system in the field of HPLC, UHPLC and nano and micro HPLC for the pulsation-free conveying and accurate mixing of solvents and a method to quickly adjust mixing ratios of different solvents with different compressibilities even at very high pressure, the Repeat accuracy of gradients and handling to improve and enable new uses.
  • UHPLC Ultra High Performance Liquid Chromotography
  • the object of the invention is therefore to provide a syringe pump system for HPLC which operates essentially without pulsation, is suitable for gradient operation and carries out a desired gradient profile accurately and reproducibly even at very high pressure.
  • a syringe pump system for HPLC with at least two solvents in which two independent syringe plunger pumps are coupled to a binary system, each syringe plunger pump having a pump head, which via a respective output connecting line, which is provided with a passive pump outlet valve, a Suction line and a wash output line is connected to a multi-position valve, each multiposition valve each having a further output line, which opens into a single output line via a connection means, and the pressure required for a chromatographic analysis for each of the solvents due to the passive pump output valve separately in the respective Pump head is constructed over the pump piston.
  • the different solvents required for gradient operation are independently compressed by the respective passive pump output valves as passive check valves, so that the solvent combining via the connection means, e.g. a T-piece can be done only at the same pressure.
  • the target pressure is quickly reached by a default with higher flow rate.
  • each of the syringe plunger pumps has a motor as a drive for the piston and as a force sensor for the compression of the respective solvent.
  • a control unit is additionally provided, wherein the motor detects together with the control unit air bubbles, the compressibility of the solvent and leaks.
  • the invention also relates to a method for the pulsation-free conveying and accurate mixing of at least two solvents for HPLC in gradient operation, in which connected in a syringe pump system with two independent syringe plunger pumps each of the pump heads with a multi-position valve, flushed by means of this via separate lines and is operated closed and via a passive pump outlet valve, so that the required for the gradient operation pressure build-up in the respective pump head and the mixing of the solvent takes place only when reaching a same pressure in a connecting means.
  • the change of the solvent and the rinsing of the syringe pump heads is carried out by separate inputs and outputs in the flow through the Multiposi- tion high-pressure valve, which can close the pump head and open the passive pump outlet valve or check valve.
  • the multiposition high-pressure valve is therefore also referred to as an active multiposition high-pressure valve.
  • the pressure builds up synchronously in the respective syringe plunger pumps.
  • the pistons of the syringe plunger pumps are each driven by a motor whose motor force is measured separately, and that the solvent pressure in the pump heads behaves substantially in proportion to the engine power.
  • the drive motor can serve as a force sensor and still have a high-resolution position detection and position control.
  • the syringe plunger pumps are reinitialized for each individual HPLC analysis, thereby providing the same starting conditions for syringe plunger pumps and chromatographic analysis.
  • the invention further relates to the use of the syringe pump system, as described above and the said method in its different embodiments in the field of HPLC, UHPLC and nano and micro HPLC.
  • the syringe pump system according to the invention in one of its embodiments is not only suitable for gradient elution, but can also be used for the isocratic elution with two independent isocratic pumps and in the continuous flow mode.
  • FIG. 1 shows a schematic representation of a binary fuel jet pump system according to the invention
  • FIG. 1 shows an active multiposition valve in a functional position for an ejection movement of the syringe piston in the flushing process of the pump head
  • FIG. 2c shows a detail according to FIG. 1, which shows an active multiposition valve in a functional position in which the pump head is closed
  • FIG. 2d shows a section according to FIG. 1, which shows an active multiposition valve in a functional position, in which FIG a solvent can be forced into an outlet connection line and through a mixing tee through an outlet line.
  • a binary syringe pump system is shown with syringe plunger pumps that is suitable for a gradient operation and two separate, independent pump units 1, 1 'has.
  • These two pump units 1, respectively have drive motors, hereinafter referred to as motors 3, 3 ', with a ball screw 5, 5', which forms the respective motor axis, and a ball nut 7, 7 'with a drive carriage 9, 9 'and a pump piston 11, 1 ⁇ moves in the axial direction.
  • a pump head designated by the reference numeral 13, 13 ' is sealed with piston seals 15, 15'.
  • Each of the pump heads 13, 13 ' is in each case connected via a suction line 17, 17', a wash outlet line 19, 19 ', via a passive pump outlet valve 21, 21' and an outlet connection line 23, 23 'to a valve, which in the context of the present invention is designated as an active multiposition valve 25, 25 '.
  • This active multi-position valve 25, 25 ' is designed as a valve with rotor and has four possible functional positions of a respective connecting groove 27, 27', which are shown in Figs. 2a - 2d and are explained below.
  • FIGS. 2a and 2b which describe a rinsing process of the pump head 13, 13 '.
  • the rinsing process takes place, on the one hand, by an ejection movement of the pump piston 11, 11 ', in which the multiposition valve 25 activates the connecting groove 27 at a position which is designated A in FIG. 2a, and, on the other hand, by a suction movement of the pump piston 11, 11 ', in which the connecting groove 27 of the multiposition Valve 25 is activated in a position which Fig. 2b denotes B.
  • FIG. 2c another position is shown, in which the connecting groove 27, 27 'of the multi-position valve 25, 25' may be located and which is designated in Fig. 2c with C.
  • the pump head 20, 20 ' is closed, and it will now by means of motor control and force measurement of motor 3, 3' a possible air entrapment, the compressibility of the solvent and each of the tightness of the piston seal 15, 15 ', the Spülansaugan gleiches 29, 29 'and the Spülauscetan gleiches 31, 3, the suction line 17, 17', the output connection line 23, 23 ', the wash outlet line 19, 19', the connections on the passive pump outlet valve 21, 21 'and the Multipositi- onsventil 25, 25th ' detected.
  • the motor 3, 3 ' serves in this way simultaneously as a force sensor, which together with a control unit in the closure of the pump head 20, 20' in the position C of the connecting groove 27, 27 'of the multi-position valve 25, 25' air entrapments, the compressibility and possible leaks detected.
  • the control unit is designed as a high-resolution position detection and position control, which is not shown separately as such again.
  • the different solvents required for gradient operation in the binary syringe pump system according to the invention are compressed independently of one another in the two separate, independent pump units 1, 1 'by means of the passive pump outlet valves 21, 21', which act as check valves, so that the merging the solvent is only at the same pressure.
  • the desired target pressure is achieved quickly by setting with higher capacity.
  • each of the pump heads 13, 13 'in each case via a suction line 17, 17', a wash outlet line 19, 19 ', via a passive pump outlet valve 21, 21' and an output connection line 23, 23 'with the active Multiposi- tion valve 25, 25th Solvents may change as well Rinsing of the pump heads 13, 13 'by separate inputs and outputs in the flow through the multi-position valve 25, 25' take place, which is also referred to as multi-position high-pressure valve 25, 25 '. It is referred to as active because, among other things, it can close the pump head 13, 13 ', which is in each case in communication with it, and can open it via the passive check valve.
  • the pump heads 13, 13 'of the syringe pump system can be thermally stabilized.
  • materials are used which do not alter and thereby falsify the desired analytical results.

Landscapes

  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • Analytical Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Details Of Reciprocating Pumps (AREA)
  • Reciprocating Pumps (AREA)
  • Control Of Positive-Displacement Pumps (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

The invention describes a high-pressure syringe pump system for use in the field of HPLC, UHPLC, micro-HPLC and nano-HPLC in gradient operation. The different solvents are compressed independently by passive non-return valves, the solvent combination does not take place until at an identical pressure, and the target pressure for the initialization is achieved by a control setting with a higher delivery capacity, in which the compressibility is also taken into consideration. The changing of solvents and the flushing of the pump heads take place by way of separate inlets and outlets in the throughflow via an active multiple-position high-pressure valve which can also close the pump head and can open it via the passive non-return valve. The regulating unit and the drive motor which also serves as force sensor detect compressibility, air inclusions and leaks. Depending on the embodiment, the syringe pump heads are stabilized thermally.

Description

Spritzenpumpensystem für ein pulsationsfreies Dosieren und genaues Mischen in der HPLC, UHPLC, Nano- und Mikro-HPLC  Syringe pump system for pulsation-free dosing and accurate mixing in HPLC, UHPLC, nano- and micro-HPLC
Die Erfindung betrifft ein Spritzenpumpensystem im Bereich der HPLC, der UHPLC sowie der Nano- und Mikro-HPLC für das pulsationsfreie Fördern und genaue Mischen von Lösungsmitteln und ein Verfahren, um Mischungsverhältnisse von unterschiedlichen Lösungsmitteln mit unterschiedlichen Kompressibilitäten auch bei sehr hohem Druck schnell einzustellen, die Wiederhol-Genauigkeit von Gradienten und das Handling zu verbessert und neue Verwendungen zu ermöglichen. The invention relates to a syringe pump system in the field of HPLC, UHPLC and nano and micro HPLC for the pulsation-free conveying and accurate mixing of solvents and a method to quickly adjust mixing ratios of different solvents with different compressibilities even at very high pressure, the Repeat accuracy of gradients and handling to improve and enable new uses.
In der HPLC geht der Trend zu immer größerem Probendurchsatz bei immer kleineren Probenvolumina. Unter der „Ultra High Performance Liquid Chroma- tography" (UHPLC) versteht man entsprechend eine HPLC mit stark gesteigerter Leistung. Die Reduktion des Säulendurchmessers ging in ihrer Entwicklung noch weiter und hat darüber hinaus zur Entwicklung der Nano- und Mikro-HPLC geführt. In HPLC, the trend is towards ever greater sample throughput with smaller and smaller sample volumes. Accordingly, "Ultra High Performance Liquid Chromotography" (UHPLC) is understood to mean HPLC with greatly enhanced performance, and the reduction in column diameter has continued in development and has further led to the development of nano- and micro-HPLC.
Für das Fördern von Lösungsmitteln im Bereich der HPLC, der UHPLC sowie der Nano- und Mikro-HPLC werden seit langem große Anstrengungen unternommen, um mit möglichst geringem Aufwand exakte und reproduzierbare Resultate zu erzielen. Herkömmliche Pumpensysteme für den Bereich der HPLC, der UHPLC sowie der Nano- und Mikro-HPLC sind sehr aufwendig und meist für die Dauerforderung gebaut. Sie benötigen daher spezielle Vorkehrungen um die Pulsation, welche von den Pumpenkolbenbewegungen verursacht werden, zu dämpfen. Bei solchen Pul- sationen handelt es sich um Abweichungen von dem mittleren Druckfluß, die zu Druckschwankungen in dem HPLC-System führen. Insbesondere bei der Nano- und Mikro-HPLC können schon kleine Druckschwankungen erhebliche Fehler verursachen. For the promotion of solvents in the field of HPLC, UHPLC and nano- and micro-HPLC great efforts have been made for a long time to achieve exact and reproducible results with the least possible effort. Conventional pump systems for the field of HPLC, UHPLC and nano- and micro-HPLC are very complex and usually built for the duration of demand. They therefore require special provisions to dampen the pulsation caused by the pump piston movements. Such pulsations are deviations from the mean pressure flow, which lead to pressure fluctuations in the HPLC system. Especially in nano- and micro-HPLC even small pressure fluctuations can cause significant errors.
Außerdem hat speziell bei kleinen Flußraten von wenigen nl/min bis zu 5 ml/min und hohen Drücken bis über 1000 bar die unterschiedliche Kompressibilität von verwendeten, voneinander unterschiedlichen Lösungsmitteln oder von Lösungsmitteln mit unterschiedlicher Gassättigung einen direkten Einfluß auf die Mischgenauigkeit und die Zeit welche für die Systemequilibrierung benötigt wird. Herkömmliche Spritzenpumpen sind meist nicht für den Gradientenbetrieb, kleine Flußraten und für hohe Drücke gebaut. Die Kompressibilität der Lösungsmittel und die Mischgenauigkeit werden daher nicht oder nur sehr ungenügend berücksichtigt. Bei der Gradienten-Elution mit einem Hochdruckgradienten werden in der Regel zumindest zwei Pumpen verwendet. Bei dem Gradientendesign spielt die Art der gewählten Lösungsmittel für die Mischgenauigkeit eine große Rolle. Werden beispielsweise Methanol-Wasser-Gemische verwendet, ist schon die Mischungsreaktion stark exotherm. Es tritt eine Volumenverminderung und eine Viskositätser- höhung und Druckerhöhung ein.  In addition, especially at low flow rates of a few nl / min up to 5 ml / min and high pressures up to 1000 bar, the different compressibility of used, different solvents or solvents with different gas saturation directly affect the mixing accuracy and the time for the system equilibration is needed. Conventional syringe pumps are usually not designed for gradient operation, small flow rates, and high pressures. The compressibility of the solvents and the mixing accuracy are therefore not or only very insufficiently taken into account. Gradient elution with a high pressure gradient typically uses at least two pumps. With gradient design, the type of solvents chosen plays a major role in mixing accuracy. For example, if methanol-water mixtures used, even the mixing reaction is highly exothermic. There is a decrease in volume and a viscosity increase and pressure increase.
Bei einem anderen Gradientendesign, wie z.B. Acetonitril und Wasser, sind solche Auswirkungen weniger stark vorhanden und damit weniger gravierend.  In another gradient design, e.g. Acetonitrile and water, such effects are less prevalent and therefore less serious.
An das Pumpensystem werden somit hohe Anforderungen gestellt. So sollte eine konstante und reproduzierbare Fließgeschwindigkeit gewährleistet werden, weil davon die Reproduzierbarkeit der Messung abhängig ist. Es muß außerdem ein möglichst pulsationsfreier Fluß gewährleistet sein. Druckstöße könnten sogar die stationäre Phase schädigen. Bei herkömmlichen Systemen kann die dargestellte Problematik nicht oder nur unzureichend aufgefangen und berücksichtigt werden. High demands are placed on the pump system. Thus, a constant and reproducible flow rate should be ensured, because it depends on the reproducibility of the measurement. It must also be guaranteed as pulsation as possible flow. Pressure surges could even damage the stationary phase. In conventional systems, the problems presented can not or only insufficiently absorbed and taken into account.
Davon ausgehend liegt der Erfindung daher die Aufgabe zugrunde, ein Spritz- pumpensystem für die HPLC bereitzustellen, welches im wesentlichen pulsati- onsfrei arbeitet, für den Gradientenbetrieb geeignet ist und auch bei sehr hohem Druck ein gewünschtes Gradientenprofil genau und reproduzierbar ausführt. On this basis, the object of the invention is therefore to provide a syringe pump system for HPLC which operates essentially without pulsation, is suitable for gradient operation and carries out a desired gradient profile accurately and reproducibly even at very high pressure.
Gelöst wird diese Aufgabe durch ein Spritzenpumpensystem für die HPLC mit zumindest zwei Lösungsmitteln, bei dem zwei voneinander unabhängige Spritzenkolbenpumpen zu einem binären System gekoppelt sind, wobei jede Spritzenkolbenpumpe einen Pumpenkopf aufweist, der über jeweils eine Ausgangsverbindungsleitung, die mit einem passiven Pumpenausgangsventil versehen ist, eine Ansaugleitung und eine Waschausgangsleitung mit einem Multipositionsventil verbunden ist, wobei jedes Multipositionsventil jeweils eine weitere Ausgangsleitung aufweist, die über ein Verbindungsmittel in eine einzige Ausgangsleitung mündet, und der für eine chromatographische Analyse erforderliche Druck für jedes der Lösungsmittel aufgrund des passiven Pumpenausgangsventils jeweils separat in dem jeweiligen Pumpenkopf über den Pumpenkolben aufgebaut ist. This object is achieved by a syringe pump system for HPLC with at least two solvents, in which two independent syringe plunger pumps are coupled to a binary system, each syringe plunger pump having a pump head, which via a respective output connecting line, which is provided with a passive pump outlet valve, a Suction line and a wash output line is connected to a multi-position valve, each multiposition valve each having a further output line, which opens into a single output line via a connection means, and the pressure required for a chromatographic analysis for each of the solvents due to the passive pump output valve separately in the respective Pump head is constructed over the pump piston.
Erfindungsgemäss werden somit die für den Gradientenbetrieb benötigten unterschiedlichen Lösungsmittel durch die jeweiligen passiven Pumpenausgangsventile als passiven Rückschlagventilen unabhängig komprimiert, so daß die Lösungsmittelzusammenführung über das Verbindungsmittel, welches z.B. ein T-Stück sein kann, erst bei gleichem Druck erfolgt. Thus, according to the invention, the different solvents required for gradient operation are independently compressed by the respective passive pump output valves as passive check valves, so that the solvent combining via the connection means, e.g. a T-piece can be done only at the same pressure.
Bei dem erfindungsgemäßen Spritzenpumpensystem wird der Zieldruck durch eine Vorgabe mit höherer Förderleistung schnell erreicht.  In the syringe pump system according to the invention, the target pressure is quickly reached by a default with higher flow rate.
Des weiteren kann bei dem Spritzenpumpensystem vorgesehen sein, daß jede der Spritzenkolbenpumpen einen Motor als Antrieb für den Kolben und als Kraftsensor für die Kompression des jeweiligen Lösungsmittels aufweist. Bevorzugt ist zusätzlich eine Regeleinheit vorgesehen, wobei der Motor zusammen mit der Regeleinheit Lufteinschlüsse, die Kompressibilität des Lösungsmittels und Undichtigkeiten erfaßt. Furthermore, it may be provided in the syringe pump system that each of the syringe plunger pumps has a motor as a drive for the piston and as a force sensor for the compression of the respective solvent. Preferably, a control unit is additionally provided, wherein the motor detects together with the control unit air bubbles, the compressibility of the solvent and leaks.
Die Erfindung betrifft auch ein Verfahren für das pulsationsfreie Fördern und genaue Mischen von zumindest zwei Lösungsmitteln für die HPLC im Gradientenbetrieb, bei dem in einem Spritzenpumpensystem mit zwei voneinander unabhängigen Spritzenkolbenpumpen jeder der Pumpenköpfe mit einem Multipositions- ventil verbunden, mittels diesem über voneinander getrennte Leitungen gespült und verschlossen und über ein passives Pumpenausgangsventil betrieben wird, so daß der für den Gradientenbetrieb erforderliche Druckaufbau in dem jeweiligen Pumpenkopf und die Vermischung der Lösungsmittel erst bei Erreichen eines gleichen Drucks in einem Verbindungsmittel erfolgt. The invention also relates to a method for the pulsation-free conveying and accurate mixing of at least two solvents for HPLC in gradient operation, in which connected in a syringe pump system with two independent syringe plunger pumps each of the pump heads with a multi-position valve, flushed by means of this via separate lines and is operated closed and via a passive pump outlet valve, so that the required for the gradient operation pressure build-up in the respective pump head and the mixing of the solvent takes place only when reaching a same pressure in a connecting means.
Das Wechseln der Lösungsmittel sowie das Spülen der Spritzenpumpenköpfe erfolgt dabei durch getrennte Ein- und Ausgänge im Durchfluß über das Multiposi- tions-Hochdruckventil, welches den Pumpenkopf verschließen und über das passive Pumpenausgangsventil oder Rückschlagventil öffnen kann. Das Multipositi- ons-Hochdruckventil wird deshalb auch als aktives Multipositions- Hochdruckventil bezeichnet. The change of the solvent and the rinsing of the syringe pump heads is carried out by separate inputs and outputs in the flow through the Multiposi- tion high-pressure valve, which can close the pump head and open the passive pump outlet valve or check valve. The multiposition high-pressure valve is therefore also referred to as an active multiposition high-pressure valve.
Vorzugsweise baut sich der Druck in den jeweiligen Spritzenkolbenpumpen synchron auf. Preferably, the pressure builds up synchronously in the respective syringe plunger pumps.
Des weiteren kann vorgesehen sein, daß die Kolben der Spritzenkolbenpumpen jeweils über einen Motor angetrieben werden, dessen Motorkraft separat gemessen wird, und daß sich der Lösungsmitteldruck in den Pumpenköpfen im wesentlichen proportional zu der Motorkraft verhält. Furthermore, it can be provided that the pistons of the syringe plunger pumps are each driven by a motor whose motor force is measured separately, and that the solvent pressure in the pump heads behaves substantially in proportion to the engine power.
Der Antriebsmotor kann dabei als Kraftsensor dienen und noch eine hochauflösende Positionserkennung und Positionsregelung aufweisen. Vorzugsweise werden die Spritzenkolbenpumpen für jede einzelne HPLC- Analyse neu initialisiert, so daß dadurch jeweils gleiche Startbedingungen für die Spritzenkolbenpumpen und chromatographische Analyse gegeben sind. Die Erfindung betrifft des weiteren die Verwendung des Spritzenpumpensystems, wie zuvor beschrieben und des genannten Verfahrens in seinen unterschiedlichen Ausgestaltungen im Bereich der HPLC, der UHPLC sowie der Nano- und Mikro- HPLC. The drive motor can serve as a force sensor and still have a high-resolution position detection and position control. Preferably, the syringe plunger pumps are reinitialized for each individual HPLC analysis, thereby providing the same starting conditions for syringe plunger pumps and chromatographic analysis. The invention further relates to the use of the syringe pump system, as described above and the said method in its different embodiments in the field of HPLC, UHPLC and nano and micro HPLC.
Dabei sind Untersuchungen mit Gradienten und im wesentlichen pulsationsfreiem Fluß für HPLC-Säulen mit 2.1mm bis 150um möglich.  In this case, studies with gradients and essentially pulsation-free flow for HPLC columns with 2.1mm to 150um are possible.
Das erfindungsgemäße Spritzenpumpensystem in einer seiner Ausgestaltungen ist jedoch nicht nur für die Gradienten-Elution einsetzbar, sondern kann genauso für die isokratische Elution mit zwei voneinander unabhängigen isokratischen Pum- pen und im continous flow-Modus eingesetzt werden. However, the syringe pump system according to the invention in one of its embodiments is not only suitable for gradient elution, but can also be used for the isocratic elution with two independent isocratic pumps and in the continuous flow mode.
Im folgenden soll die Erfindung anhand eines Ausführungsbeispiels unter Bezugnahme auf die Fig. der Zeichnung näher erläutert werden. In the following the invention with reference to an embodiment with reference to the Fig. The drawing will be explained in more detail.
Es zeigen: Show it:
Fig. 1 : Eine schematische Darstellung eines erfindungsgemäßen binären Sprit- zenkolbenpumpensystems, 1 shows a schematic representation of a binary fuel jet pump system according to the invention,
Fig. 2a: einen Ausschnitt nach Fig. 1, der ein aktives Multipositionsventil in einer Funktionsstellung zeigt für eine Ausstoßbewegung des Spritzenkolbens bei dem Spülvorgang des Pumpenkopfs, einen Ausschnitt nach Fig. 1, der ein aktives Multipositionsventil in einer Funktionsstellung zeigt für eine Ansaugbewegung des Spritzenkolbens bei dem Spülvorgang des Pumpenkopfs, Fig. 2c: einen Ausschnitt nach Fig. 1 , der ein aktives Multipositionsventil in einer Funktionsstellung zeigt, in der der Pumpenkopf verschlossen ist, und Fig. 2d: einen Ausschnitt nach Fig. 1, der ein aktives Multipositionsventil in einer Funktionsstellung zeigt, in der ein Lösungsmittel in eine Ausgangsverbindungsleitung und über ein Misch-T-Stück durch eine Ausgangsleitung gedrückt werden kann. 1, which shows an active multiposition valve in a functional position for an ejection movement of the syringe piston in the flushing process of the pump head, a detail of FIG. 1, which shows an active multi-position valve in a functional position for a suction movement of the syringe plunger in the flushing process of the pump head, FIG. 2c shows a detail according to FIG. 1, which shows an active multiposition valve in a functional position in which the pump head is closed, and FIG. 2d shows a section according to FIG. 1, which shows an active multiposition valve in a functional position, in which FIG a solvent can be forced into an outlet connection line and through a mixing tee through an outlet line.
In Fig. 1 ist ein binäres Spritzenpumpen-System mit Spritzenkolbenpumpen dargestellt, daß für einen Gradientenbetrieb geeignet ist und zwei voneinander getrennte, unabhängige Pumpeneinheiten 1 , 1 ' aufweist. Diese beiden Pumpeneinheiten 1, weisen ihrerseits jeweils Antriebsmotoren, im folgenden kurz Moto- ren 3, 3' genannt, auf, mit einer Kugelumlaufspindel 5, 5', welche die jeweilige Motorachse bildet, und eine Kugelumlaufmutter 7, 7' mit einem Antriebsschlitten 9, 9' und einen Pumpenkolben 11, 1 Γ in axialer Richtung bewegt. In Fig. 1, a binary syringe pump system is shown with syringe plunger pumps that is suitable for a gradient operation and two separate, independent pump units 1, 1 'has. These two pump units 1, in turn, respectively have drive motors, hereinafter referred to as motors 3, 3 ', with a ball screw 5, 5', which forms the respective motor axis, and a ball nut 7, 7 'with a drive carriage 9, 9 'and a pump piston 11, 1 Γ moves in the axial direction.
Ein mit der Bezugsziffer 13, 13' bezeichneter Pumpenkopf ist mit Kolbendichtungen 15, 15' abgedichtet. Jeder der Pumpenköpfe 13, 13' ist jeweils über eine Ansaugleitung 17, 17', eine Waschausgangsleitung 19, 19', über ein passives Pumpenausgangsventil 21, 21 ' und eine Ausgangsverbindungsleitung 23, 23' mit einem Ventil verbunden, das im Rahmen der vorliegenden Erfindung als ein aktives Multipositionsventil 25, 25' bezeichnet ist. Dieses aktive Multipositionsventil 25, 25' ist als Ventil mit Rotor ausgebildet und weist vier mögliche Funktionsstellungen einer jeweiligen Verbindungsnut 27, 27' auf, welche in den Fig. 2a - 2d dargestellt sind und im folgenden erläutert werden. Dabei wird zunächst auf die Fig. 2a und 2b Bezug genommen, welche einen Spülvorgang des Pumpenkopfs 13, 13' beschreiben. Der Spülvorgang erfolgt zum ei- nen durch eine Ausstoßbewegung des Pumpenkolbens 11, 11 ', bei welcher das Multipositionsventil 25 die Verbindungsnut 27 auf einer Position aktiviert, welche in Fig. 2a mit A bezeichnet ist, und zum anderen durch eine Ansaugbewegung des Pumpenkolbens 11, 11 ', bei welcher die Verbindungsnut 27 des Multipositions- ventils 25 auf einer Position aktiviert ist, die Fig. 2b mit B bezeichnet. Hierfür sind an jedem der Pumpenköpfe 13, 13' ein Spülansauganschluß 29, 29' und ein Spülausstoßanschluß 31, 31 ' an den gegenüberliegenden Enden jedes der Pumpenköpfe 13, 13' angebracht. Dadurch werden diese beim Spül Vorgang in einer Richtung durchflössen. A pump head designated by the reference numeral 13, 13 'is sealed with piston seals 15, 15'. Each of the pump heads 13, 13 'is in each case connected via a suction line 17, 17', a wash outlet line 19, 19 ', via a passive pump outlet valve 21, 21' and an outlet connection line 23, 23 'to a valve, which in the context of the present invention is designated as an active multiposition valve 25, 25 '. This active multi-position valve 25, 25 'is designed as a valve with rotor and has four possible functional positions of a respective connecting groove 27, 27', which are shown in Figs. 2a - 2d and are explained below. Reference is first made to FIGS. 2a and 2b, which describe a rinsing process of the pump head 13, 13 '. The rinsing process takes place, on the one hand, by an ejection movement of the pump piston 11, 11 ', in which the multiposition valve 25 activates the connecting groove 27 at a position which is designated A in FIG. 2a, and, on the other hand, by a suction movement of the pump piston 11, 11 ', in which the connecting groove 27 of the multiposition Valve 25 is activated in a position which Fig. 2b denotes B. For this purpose, a Spülansauganschluß 29, 29 'and a Spülausstoßanschluß 31, 31' at each of the pump heads 13, 13 'at the opposite ends of each of the pump heads 13, 13' attached to each of the pump heads. As a result, they are flowed through during the flushing process in one direction.
In Fig. 2c ist eine weitere Position dargestellt, in welcher die Verbindungsnut 27, 27' des Multipositionsventils 25, 25' sich befinden kann und die in Fig. 2c mit C bezeichnet ist. In dieser Stellung ist der Pumpenkopf 20, 20' verschlossen, und es werden nun mittels der Motorsteuerung und Kraftmessung von Motor 3, 3' ein möglicher Lufteinschluss, die Kompressibilität des Lösungsmittels sowie jeweils die Dichtigkeit der Kolbendichtung 15, 15', des Spülansauganschlusses 29, 29' und des Spülausstoßanschlusses 31, 3 , der Ansaugleitung 17, 17', der Ausgangsverbindungsleitung 23, 23', der Waschausgangsleitung 19, 19', der An- Schlüsse am passiven Pumpenausgangsventil 21, 21 ' und von dem Multipositi- onsventil 25, 25' erfaßt. In Fig. 2c, another position is shown, in which the connecting groove 27, 27 'of the multi-position valve 25, 25' may be located and which is designated in Fig. 2c with C. In this position, the pump head 20, 20 'is closed, and it will now by means of motor control and force measurement of motor 3, 3' a possible air entrapment, the compressibility of the solvent and each of the tightness of the piston seal 15, 15 ', the Spülansauganschlusses 29, 29 'and the Spülausstoßanschlusses 31, 3, the suction line 17, 17', the output connection line 23, 23 ', the wash outlet line 19, 19', the connections on the passive pump outlet valve 21, 21 'and the Multipositi- onsventil 25, 25th ' detected.
Der Motor 3, 3' dient auf diese Weise gleichzeitig als Kraftsensor, der zusammen mit einer Regeleinheit bei dem Verschluß des Pumpenkopfes 20, 20' in der Position C des Verbindungsnut 27, 27' des Multipositionsventils 25, 25' Luftein- Schlüsse, die Kompressibilität und mögliche Undichtigkeiten erfaßt. Die Regeleinheit ist als hochauflösende Positionserkennung und Positionsregelung ausgebildet, was als solches nicht noch einmal gesondert dargestellt ist.  The motor 3, 3 'serves in this way simultaneously as a force sensor, which together with a control unit in the closure of the pump head 20, 20' in the position C of the connecting groove 27, 27 'of the multi-position valve 25, 25' air entrapments, the compressibility and possible leaks detected. The control unit is designed as a high-resolution position detection and position control, which is not shown separately as such again.
Erst wenn die Verbindungsnut 27, 27' des Multipositionsventils 25, 25' auf einer Position steht, wie sie in Fig. 2d mit D bezeichnet ist, kann bei positivem Kolbenhub das Lösungsmittel über das passives Pumpenausgangsventil 21, 21 ' der jeweiligen Ausgangsverbindungsleitung 23, 23' und einer jeweils weiteren Ausgangsleitung 33, 33' in ein Misch-T-Stück 35 und durch eine gemeinsame Ausgangsleitung 37 gedrückt werden. Only when the connecting groove 27, 27 'of the multi-position valve 25, 25' is in a position, as indicated in FIG. 2d with D, can the solvent via the passive pump outlet valve 21, 21 'of the respective output connection line 23, 23 and a respective further output line 33, 33 'are pressed into a mixing tee 35 and through a common output line 37.
Dabei muß je nach der verwendeten chromatographischen HPLC-Methode mit Drücken bis über 1000 bar auf der Ausgangsleitung 37 gerechnet werden. Über das passive Pumpenausgangsventil 21, 21 ' wird sichergestellt, daß bei einer unter- schiedlichen Kompressibilität der jeweiligen verwendeten Lösungsmittel in den Pumpenköpfen 13, 13' die Lösungsmittel nur durch den jeweiligen Pumpenkolben 11, 11 ' komprimiert werden und die Vermischung der beiden Lösungsmittel erst bei Erreichen des gleichen Drucks im Misch-T-Stück 35 erfolgt. Die Zeit für das Erreichen der chromatographischen Startbedingungen ist abhängig vom Druck, dem Mischungsverhältnis, der Fließgeschwindigkeit sowie der Kompressibilität der unterschiedlichen Lösungsmittel. Daher wird sich der Druck in den Pumpenköpfen 13, 13' synchron aufbauen. Erfindungsgemäß können die chromatographischen Startbedingungen wesentlich schneller und zuverlässiger erreicht werden, als dies herkömmlich im Stand der Technik möglich ist. Dies ist grundsätzlich dadurch bedingt, daß im Rahmen der vorliegenden Erfindung eine jeweils getrennte Motoren-Kraftmessung der Antriebsmotoren 3, 3' durchgeführt wird, wie oben erläutert. Hinzu kommt, daß sich außerdem bei dem erfindungsgemäßen Spritzenpumpensystem der Lösungsmitteldruck in den Pumpenköpfen 13, 13' weitgehend proportional zur Motorenkraft verhält. Auf diese Weise werden die chromatographischen Startbedingungen durch eine entsprechende Motorenregelung und eine Startdruckvorgabe wesentlich schneller erreicht. It must be expected depending on the chromatographic HPLC method used with pressures up to 1000 bar on the output line 37. Via the passive pump outlet valve 21, 21 'it is ensured that in the case of a different compressibility of the particular solvent used in the pump heads 13, 13 ', the solvent only by the respective pump piston 11, 11' are compressed and the mixing of the two solvents takes place only when the same pressure in the mixing tee 35. The time to reach the chromatographic start conditions depends on the pressure, the mixing ratio, the flow rate and the compressibility of the different solvents. Therefore, the pressure in the pump heads 13, 13 'will build up synchronously. According to the invention, the chromatographic start conditions can be achieved much faster and more reliably than is conventionally possible in the prior art. This is basically due to the fact that in the context of the present invention, a separate motor force measurement of the drive motors 3, 3 'is performed, as explained above. In addition, in addition, in the syringe pump system according to the invention, the solvent pressure in the pump heads 13, 13 'is largely proportional to the engine power. In this way, the chromatographic starting conditions are achieved much faster by a corresponding engine control and a starting pressure specification.
Die für den Gradientenbetrieb in dem erfindungsgemäßen binären Spritzenpumpen-System benötigten unterschiedlichen Lösungsmittel werden mit Hilfe der passiven Pumpenausgangsventile 21, 21 ', welche als Rückschlagventile wirken, unabhängig voneinander in den beiden voneinander getrennten, unabhängigen Pumpeneinheiten 1, 1' komprimiert, so daß die Zusammenführung der Lösungsmittel erst bei gleichem Druck erfolgt. Dabei wird der gewünschte Zieldruck durch eine Vorgabe mit höherer Förderleistung schnell erreicht. The different solvents required for gradient operation in the binary syringe pump system according to the invention are compressed independently of one another in the two separate, independent pump units 1, 1 'by means of the passive pump outlet valves 21, 21', which act as check valves, so that the merging the solvent is only at the same pressure. In this case, the desired target pressure is achieved quickly by setting with higher capacity.
Dadurch, daß jeder der Pumpenköpfe 13, 13' jeweils über eine Ansaugleitung 17, 17', eine Waschausgangsleitung 19, 19', über ein passives Pumpenausgangsventil 21, 21 ' und eine Ausgangsverbindungsleitung 23, 23' mit dem aktiven Multiposi- tionsventil 25, 25' verbunden ist, kann das Ändern von Lösungsmitteln sowie das Spülen der Pumpenköpfe 13, 13' durch getrennte Ein- und Ausgänge im Durchfluß über das Multipositionsventil 25, 25' erfolgen, das auch als Multipositions- Hochdruckventil 25, 25' zu bezeichnen ist. Als aktiv ist es bezeichnet, weil es unter anderem den jeweils mit ihm in Verbindung stehenden Pumpenkopf 13, 13' verschließen und über das passive Rückschlagventil öffnen kann. Characterized in that each of the pump heads 13, 13 'in each case via a suction line 17, 17', a wash outlet line 19, 19 ', via a passive pump outlet valve 21, 21' and an output connection line 23, 23 'with the active Multiposi- tion valve 25, 25th Solvents may change as well Rinsing of the pump heads 13, 13 'by separate inputs and outputs in the flow through the multi-position valve 25, 25' take place, which is also referred to as multi-position high-pressure valve 25, 25 '. It is referred to as active because, among other things, it can close the pump head 13, 13 ', which is in each case in communication with it, and can open it via the passive check valve.
Aufgrund des erläuterten Aufbaus des erfindungsgemäßen binäres Spritzenpumpen-Systems, bei dem jeder einzelne Pumpenkopf 13, 13' mittels des aktiven Multipositionsventils 25, 25' über die genannten separaten Leitungen gespült, verschlossen und über das passive Pumpenausgangsventil 21, 21 ', das als Rückschlagventil ausgebildet ist, betrieben wird, sich außerdem der Spülansauganschluß und die Waschausgangsleitung 19, 19' als Ausgangsspülanschluß voneinander getrennt an dem jeweiligen Pumpenkopf 13, 13' befinden, und insgesamt der Druckaufbau in dem jeweiligen Pumpenkopf 13, 13' und nur mit dem Pum- penkolben 11, 11 ' erfolgen kann, wird ebenso erreicht, daß das System im wesentlichen pulsationsfrei arbeitet. Due to the illustrated construction of the binary syringe pump system according to the invention, in which each individual pump head 13, 13 'flushed by means of the active multiposition valve 25, 25' via said separate lines, closed and via the passive pump outlet valve 21, 21 ', which designed as a check valve is, is operated, also the Spülansauganschluß and the wash outlet line 19, 19 'as Ausgangpülanschluß separated from each other on the respective pump head 13, 13' are located, and overall the pressure build-up in the respective pump head 13, 13 'and only with the pump plunger eleventh , 11 'is also achieved that the system operates substantially pulsation-free.
Zusätzlich können je nach gewünschter Ausführung die Pumpenköpfe 13, 13' des Spritzenpumpen-Systems thermisch stabilisiert werden. Es werden für die Pum- penköpfe 13, 13' Materialien verwendet, welche die gewünschten analytischen Resultate nicht verändern und dadurch verfalschen. In addition, depending on the desired embodiment, the pump heads 13, 13 'of the syringe pump system can be thermally stabilized. For the pump heads 13, 13 ', materials are used which do not alter and thereby falsify the desired analytical results.
Insbesondere bei kleinen Förderleistungen ist es von Vorteil, wenn die Pumpenköpfe 13, 13' thermisch stabilisiert sind und die Druckleitungen und das Multipositionsventil isoliert werden.  In particular, at low flow rates, it is advantageous if the pump heads 13, 13 'are thermally stabilized and the pressure lines and the multi-position valve are isolated.
Es ist außerdem möglich, daß mehrere Pumpenausgänge gekoppelt werden, wobei das jeweilige Erreichen der chromatographischen Startbedingungen einer jeder Analyse oder eines jeden Analysenlaufs durch eine Regelcharakteristik erfolgt, bei der die Kraftsensorik jeder der Spritzenkolbenpumpen den Druckaufbau und die Fördergeschwindigkeit aller gekoppelten Pumpen miteinschließt. It is also possible to couple a plurality of pump outputs, wherein the respective achievement of the chromatographic start conditions of each analysis or run is governed by a control characteristic in which the force sensor of each of the syringe plunger pumps includes the pressure build-up and rate of delivery of all the coupled pumps.

Claims

Patentansprüche claims
1. Spritzenpumpensystem für die HPLC mit zumindest zwei Lösungsmitteln, bei dem zwei voneinander unabhängige Spritzenkolbenpumpen zu einem binären System gekoppelt sind, wobei jede Spritzenkolbenpumpe einen Pumpenkopf (13, 13') aufweist, der über jeweils eine Ausgangsverbindungsleitung (23, 23'), die mit einem passiven Pumpenausgangsventil (21, 21 ') versehen ist, eine Ansaugleitung (17, 17') und eine Waschausgangsleitung (19, 19') mit einem Multipositionsventil (25, 25') verbunden ist, wobei jedes Multipositionsventil (25, 25') jeweils eine weitere Ausgangsleitung (33, 33') aufweist, die über ein Verbindungsmittel (35) in eine gemeinsame Ausgangsleitung (37) mündet, und der für eine chromatographische Analyse erforderliche Druck für jedes der Lösungsmittel aufgrund des passiven Pumpenausgangsventils (21, 2 ) jeweils separat in dem jeweiligen Pumpenkopf (13, 13') über den Pumpenkolben (11, 1 Γ) aufgebaut ist. A syringe pump system for HPLC with at least two solvents, in which two independent syringe plunger pumps are coupled to a binary system, each syringe plunger pump having a pump head (13, 13 ') connected via in each case one output connection line (23, 23') is provided with a passive pump outlet valve (21, 21 '), a suction line (17, 17') and a wash outlet line (19, 19 ') connected to a multi-position valve (25, 25'), each multiposition valve (25, 25 ' ) each having a further output line (33, 33 ') which opens via a connecting means (35) in a common output line (37), and the pressure required for a chromatographic analysis for each of the solvents due to the passive pump outlet valve (21, 2) each separately in the respective pump head (13, 13 ') via the pump piston (11, 1 Γ) is constructed.
2. Spritzenpumpensystem nach Anspruch 1, dadurch gekennzeichnet, daß jede Spritzenkolbenpumpe einen Motor (3, 3') als Antrieb für den Pumpenkolben (11, 11 ') und als Kraftsensor für die Kompression des jeweiligen Lösungsmittels aufweist. 2. syringe pump system according to claim 1, characterized in that each syringe piston pump has a motor (3, 3 ') as a drive for the pump piston (11, 11') and as a force sensor for the compression of the respective solvent.
3. Spritzenpumpensystem nach Anspruch 2, dadurch gekennzeichnet, daß zusätzlich eine Regeleinheit vorgesehen ist, und daß der Motor (3, 3') zusammen mit der Regeleinheit Lufteinschlüsse, die Kompressibilität des Lösungsmittels und Undichtigkeiten erfaßt. 3. syringe pump system according to claim 2, characterized in that in addition a control unit is provided, and that the motor (3, 3 ') detects together with the control unit air pockets, the compressibility of the solvent and leaks.
4. Verfahren für das pulsationsfreie Fördern und genaue Mischen von zumindest zwei Lösungsmitteln für die HPLC im Gradientenbetrieb, bei dem in einem Spritzenpumpensystem mit zwei voneinander unabhängigen Spritzen- kolbenpumpen jeder der Pumpenköpfe (13, 13') mit einem Multipositions- ventil (25, 25') verbunden, mittels diesem über voneinander getrennte Leitungen gespült und verschlossen und über ein passives Pumpenausgangsventil (21, 2 ) betrieben wird, so daß der für den Gradientenbetrieb erforderliche Druckaufbau in dem jeweiligen Pumpenkopf (13, 13') erfolgt und die Vermischung der Lösungsmittel erst bei Erreichen eines gleichen Drucks in einem Verbindungsmittel erfolgt. 4. Process for the pulsation-free pumping and accurate mixing of at least two solvents for HPLC in gradient mode, in which in a syringe pump system with two independent syringes piston pump each of the pump heads (13, 13 ') with a multi-position valve (25, 25'), flushed by means of this via separate lines and closed and operated by a passive pump outlet valve (21, 2), so that for the Gradient operation required pressure build-up in the respective pump head (13, 13 ') takes place and the mixing of the solvent takes place only when reaching a same pressure in a connecting means.
5. Verfahren nach Anspruch 4, dadurch gekennzeichnet, daß sich der Druck in den jeweiligen Spritzenkolbenpumpen synchron aufbaut. 5. The method according to claim 4, characterized in that the pressure builds up synchronously in the respective syringe plunger pumps.
6. Verfahren nach Anspruch 4 oder 5, dadurch gekennzeichnet, daß die Kolben (11, 11 ') der Spritzenkolbenpumpen jeweils über einen Motor (3, 3') angetrieben werden, dessen Motorkraft separat gemessen wird, und daß sich der Lösungsmitteldruck in den Pumpenköpfen (13, 13') im wesentlichen proportional zu der Motorkraft verhält. 6. The method according to claim 4 or 5, characterized in that the pistons (11, 11 ') of the syringe plunger pumps in each case via a motor (3, 3') are driven, whose motor force is measured separately, and that the solvent pressure in the pump heads (13, 13 ') is substantially proportional to the engine power.
7. Verfahren nach einem der Ansprüche 4 bis 6, dadurch gekennzeichnet, daß die Spritzenkolbenpumpen für jede einzelne HPLC-Analyse neu initialisiert und dadurch jeweils gleiche Startbedingungen für die Spritzenkolbenpumpen und chromatographische Analyse gegeben sind. 7. The method according to any one of claims 4 to 6, characterized in that the syringe plunger pumps reinitialized for each individual HPLC analysis and thereby each same starting conditions for the syringe plunger pumps and chromatographic analysis are given.
8. Verwendung des Spritzenpumpensystems nach einem der Ansprüche 1 bis 3 und des Verfahrens nach einem der Ansprüche 4 bis 7 im Bereich der HPLC, der UHPLC sowie der Nano- und Mikro-HPLC. 8. Use of the syringe pump system according to one of claims 1 to 3 and the method according to one of claims 4 to 7 in the field of HPLC, UHPLC and nano and micro HPLC.
9. Verwendung des Spritzenpumpensystems nach einem der Ansprüche 1 bis 3 für die Gradienten-Elution, die isokratische Elution und im continous flow- Modus. 9. Use of the syringe pump system according to any one of claims 1 to 3 for the gradient elution, the isocratic elution and in the continuous flow mode.
EP13789166.9A 2012-09-11 2013-09-11 Syringe pump for pulsation free dosing and precise mixing in hplc, uhplc, micro- and nano-hplc Active EP2895744B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH01653/12A CH706929A1 (en) 2012-09-11 2012-09-11 Ultra-high-pressure syringe pump system for the gradient operation in the field of HPLC.
PCT/EP2013/002728 WO2014040727A1 (en) 2012-09-11 2013-09-11 Syringe pump system for pulse-free metering and precise mixing in hplc, uhplc, micro-hplc and nano-hplc

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EP13789166.9A Active EP2895744B1 (en) 2012-09-11 2013-09-11 Syringe pump for pulsation free dosing and precise mixing in hplc, uhplc, micro- and nano-hplc

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EP (1) EP2895744B1 (en)
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Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH709709A1 (en) * 2014-05-30 2015-11-30 Werner Döbelin System configuration for the injection of samples with automatic solid phase extraction with a single binary pump system to operate in the field of HPLC, ultra-, micro- and nano-HPLC.
DE102018104842A1 (en) * 2018-03-02 2018-04-19 Agilent Technologies, Inc. - A Delaware Corporation - Fluid mixing by means of fluid supply lines with line-specific associated fluid pumps for liquid chromatography
ES2915839T3 (en) 2019-06-04 2022-06-27 Hoffmann La Roche Rapid Liquid Exchange in Liquid Chromatography
CN113495165A (en) * 2020-04-02 2021-10-12 中国科学院深圳先进技术研究院 Continuous liquid sampling system and control method thereof
CN114352499B (en) * 2022-01-11 2022-10-14 重庆通用工业(集团)有限责任公司 Air supplement mixing anti-surge control method for compressor

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3446057A (en) * 1966-10-14 1969-05-27 Varian Associates Method and apparatus for chromatography
US3855129A (en) * 1972-03-06 1974-12-17 Waters Associates Inc Novel pumping apparatus
US3816029A (en) * 1972-10-03 1974-06-11 Duriron Co Pumping unit for constant pulseless flow
US4032445A (en) * 1975-11-10 1977-06-28 Varian Associates Liquid chromatography pumping system with compensation means for liquid compressibility
JPS52133294A (en) * 1976-05-01 1977-11-08 Nippon Bunko Kogyo Kk Pumping system and liquid transfer process for liquid chromatography
US4225290A (en) * 1979-02-22 1980-09-30 Instrumentation Specialties Company Pumping system
US4242909A (en) * 1979-04-19 1981-01-06 Rheodyne Incorporated Sample injector
US4255088A (en) * 1979-06-14 1981-03-10 Valleylab, Inc. Liquid pumping system having means for detecting gas in the pump
US4321014A (en) * 1979-12-31 1982-03-23 Polaroid Corporation Constant flow pumping apparatus
US4347131A (en) * 1981-04-28 1982-08-31 Robert Brownlee Liquid chromatographic pump module
US4566858A (en) * 1981-10-08 1986-01-28 Nikkiso Co., Ltd. Pulsation-free volumetric pump
US4915591A (en) * 1986-01-08 1990-04-10 Saphirwerk Industrieprodukte Ag Reciprocating pump and control using outlet valve position sensors
US4714545A (en) * 1986-03-20 1987-12-22 Hewlett-Packard Company Fluid proportioning pump system
JPS63173866A (en) * 1987-01-09 1988-07-18 Hitachi Ltd Controlling system for nonpulsation pump
US4753581A (en) * 1987-02-10 1988-06-28 Milton Roy Company Constant suction pump for high performance liquid chromatography
EP0327658B1 (en) * 1988-02-11 1991-10-23 Hewlett-Packard GmbH Sample injector for a liquid chromatograph
US5360320A (en) * 1992-02-27 1994-11-01 Isco, Inc. Multiple solvent delivery system
US5253981A (en) * 1992-03-05 1993-10-19 Frank Ji-Ann Fu Yang Multichannel pump apparatus with microflow rate capability
JP3491948B2 (en) * 1993-03-05 2004-02-03 ウォーターズ・インベストメンツ・リミテッド Solvent pump feeder
FR2726332B1 (en) * 1994-10-26 1997-01-24 Francois Couillard PISTON PUMPING SYSTEM DELIVERING FLUIDS WITH SUBSTANTIALLY CONSTANT FLOW RATE
US5814742A (en) * 1996-10-11 1998-09-29 L C Packings, Nederland B.V. Fully automated micro-autosampler for micro, capillary and nano high performance liquid chromatography
US5897781A (en) * 1997-06-06 1999-04-27 Waters Investments Limited Active pump phasing to enhance chromatographic reproducibility
US6155123A (en) * 1998-04-17 2000-12-05 Rheodyne, L.P. Multivalving sample injection system
DK1194200T3 (en) * 1999-04-23 2009-05-04 Advion Biosystems Inc Parallel fluid flow chromatography system with high throughput
US6672336B2 (en) * 2001-11-28 2004-01-06 Rheodyne, Lp Dual random access, three-way rotary valve apparatus
US6712587B2 (en) * 2001-12-21 2004-03-30 Waters Investments Limited Hydraulic amplifier pump for use in ultrahigh pressure liquid chromatography
US6998095B2 (en) * 2003-08-15 2006-02-14 Metara, Inc. Loop dilution system
JP4077674B2 (en) * 2002-07-24 2008-04-16 憲一 工藤 Gradient liquid feeding device and liquid feeding method for nano / micro liquid chromatograph
JP4206308B2 (en) * 2003-08-01 2009-01-07 株式会社日立ハイテクノロジーズ Liquid chromatograph pump
JP4377639B2 (en) * 2003-09-18 2009-12-02 株式会社日立ハイテクノロジーズ Pumps and liquid pumps for chromatography
DE112005000331B4 (en) * 2004-03-05 2019-03-28 Waters Technologies Corp. (N.D.Ges.D. Staates Delaware) Optimized high performance liquid chromatography sample introduction with bubble detection
US20050214130A1 (en) * 2004-03-29 2005-09-29 Yang Frank J Multidimensional pump apparatus and method for fully automated complex mixtures separation, identification, and quantification
WO2007051113A2 (en) * 2005-10-27 2007-05-03 Waters Investments Limited Pump
US20100262381A1 (en) * 2007-06-29 2010-10-14 Zeng William B Method of manufacturing and testing solid dosage products and apparatus for the testing
DE102007059651B4 (en) * 2007-12-10 2017-05-24 Dionex Softron Gmbh Sampler for high performance liquid chromatography
WO2009098125A1 (en) * 2008-02-06 2009-08-13 Proxeon Biosystems A/S Flow control in high performance liquid chromatography
CH699313A1 (en) * 2008-08-15 2010-02-15 Ctc Analytics Ag Sample introduction device.
EP2524230A4 (en) * 2010-01-13 2013-07-24 Nomadics Inc In situ-dilution method and system for measuring molecular and chemical interactions
CH703256A1 (en) * 2010-06-04 2011-12-15 Werner Doebelin Method and apparatus for automatic and direct analysis of dried blood spots samples by LC-MS system.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2014040727A1 *

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US20150345484A1 (en) 2015-12-03
EP2895744B1 (en) 2016-08-24
WO2014040727A1 (en) 2014-03-20
CH706929A1 (en) 2014-03-14

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